Journal article
Evolution and transmission of stable CTL escape mutations in HIV infection
Nature, Vol.412(6844), pp.334-338
2001
Abstract
Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother–child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we document transmission of viruses encoding CTL escape variants in this dominant Gag epitope that no longer bind to B27. Their infected infants target an otherwise subdominant B27-restricted epitope and fail to contain HIV replication. These CTL escape variants remain stable without reversion in the absence of the evolutionary pressure that originally selected the mutation. These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.
Details
- Title
- Evolution and transmission of stable CTL escape mutations in HIV infection
- Authors/Creators
- P.J.R. Goulder (Author/Creator)C. Brander (Author/Creator)Y. Tang (Author/Creator)C. Tremblay (Author/Creator)R.A. Colbert (Author/Creator)M.M. Addo (Author/Creator)E.S. Rosenberg (Author/Creator)T.T. Nguyen (Author/Creator)R. Allen (Author/Creator)A. Trocha (Author/Creator)M. Altfeld (Author/Creator)S. He (Author/Creator)M. Bunce (Author/Creator)R. Funkhouser (Author/Creator)S.I. Pelton (Author/Creator)S.K. Burchett (Author/Creator)K. McIntosh (Author/Creator)B.T.M. Korber (Author/Creator)B.D. Walker (Author/Creator)
- Publication Details
- Nature, Vol.412(6844), pp.334-338
- Publisher
- Nature Publishing Group
- Identifiers
- 991005541917207891
- Copyright
- 2001 Macmillan Magazines Ltd.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology